Pediatric hepatologists in the Joint Program in Pediatric Gastroenterology, Hepatology and Nutrition at the University of California, San Diego propose their inclusion as a Clinical Center in the "Clinical Research Network in Non-Alcoholic Steatohepatitis". Although NASHgenerally is regarded as a common condition in adults, recent research reveals that NASHis one of the most common causes of liver disease in 10-18 year olds. This application proposes UCSD participation as a center on the basis of past experience of the Principal Investigator with pediatric NASH, the number of children available to our center for studies, and the ethnic diversity of our population basedon our unique geographic location. Cooperation of UCSD adult hepatologists and Scripps Clinic hepatologists for referral of adult patients with NASH will allow participation in proposals initiated by other centers in the clinical research network which focus on adults. Our NIH-funded General Clinical Research Center will facilitate all facets of proposed studies. Our application provides a template for preparation of a multicenter databaseand tissue/serum bank to study pediatric NASH, based on knowledge and experience of the presentation and proposed pathophysiology of the condition. Twoproposals are detailed in this application. Thefirst is a prospective, multi-center, epidemiologic analysis of factors associated with the development of NASH in obese children, evaluating the role of age. race and gender. Potential factors involved in pathogenesis will be assessed with respect to pubertal development, insulin resistance, increased exposure to mediators of inflammation, and increased indicators of oxidative stress. The second study is a prospective, multi-center, randomized, double-blind trial evaluating treatment of childhood NASHwith Vitamin Eversus placebo. Children randomized to placebo will serve as a long-term cohort to understand the natural history of this untreated condition with early onset. The treated children, who in previous open-label pilot studies have been shown to normalize serum markers of liver damage, will be rigorously studied to determine if antioxidant therapy improves outcome as assessedby changes in liver histology and markersfound associatedwith NASH pathogenesis.